1. Field of Invention
This invention generally relates to a patch for dispensing parenteral fluid medication through the skin and more particularly to a patch with one or more internal reservoirs which after adhesion to the skin is inert until medication is required. In general, patches have found usage for the ambulatory patient requiring an extended regimen such as for a chronic condition or for birth control. About half of all ethical pharmaceuticals are consumed for a chronic condition.
Berner & Dinh point out that many chronic conditions such as hormone deficiency would benefit from a regimen which was moderated to daily and weekly biorhythms. Chronic attacks of pain, diabetic imbalance, or panic may require intermittent medication administered to match severity and duration. Such attacks may also require involuntary administration. Attacks such as cardiovascular may require different drugs in different sequences depending upon severity.
Non-medical situations may require multiple doses on-demand during the operational life of a transdermal patch. An example of this would be a commercial pilot who may require a stimulant at intervals during a long flight to remain alert, based on automatic physiological sensing.
2. Description of the Prior Art
Prior art of on-demand transdermal therapeutic systems includes thermo-responsive membranes, user activated, and iontophoretic systems. Nozawa et al describes a liquid-crystal transdermal membrane which automatically dispenses medication when fever temperatures are reached. User activated systems such as Helber et al in U.S. Pat. No. 4,702,732 continuously medicate after manual activation. Iontophoretic systems such as Reller et al, U.S. Pat. No. 5,053,001, are only fully active when the power is turned on, but some drug exposure begins when the patch is applied.
Prior art on multi-drug systems include systems where a multi-drug mixture is packaged within the reservoir, or where the adhesive contains a medication different in composition from that in the reservoir. Hadgraft and Guy describe the former multi-drug mixture which may include a skin penetration enhancer (SPE). Sablotsky et al, U.S. Pat. No. 4,814,168, is representative of the latter where the adhesive contains a drug. This patent also represents the prior art on SPE for transdermal patches where the SPE is integral with the adhesive mastic. Such SPE adhesives are well described in Chien and Lee.
Variation in release rate has been a goal of prior art. U.S. Pat. No. 4,141,359 controls iontophoretic current and thus drug flow. Nelson et al in U.S. Pat. No. 4,917,688 varies the release rate by varying the external active exposed patch area prior to application. The difficulties of internal control of release rate prompted Helber et al in their U.S. Pat. No. 4,911,707 transdermal system patent to state in line 35 that "only a single release rate results per system." Within limits, drug concentration has an effect on skin absorption rate. None of these systems feature medication dispensing internal to the patch to allow variation in drug concentration.
Selective dispensing from multiple reservoirs has not been a goal of prior art. U.S. Pat. Nos. 4,921,475 and 5,053,001 both have multiple reservoirs for a single medication. They do not teach selective multiple drug dispensing.
Prior art on the use of colored indicators in connection with a transdermal Patch is described by Sasaki et al where phenol red was used in experiments to indicate comparative skin penetration.
Bettinger in U.S. Pat. No. 5,188,260 line 45 teaches the use of shrink-polymer dispensing for "delayed ambulatory medication." Lowry shows the shrink-polymer spectrum available.